The suprachiasmatic nucleus (SCN) of mammals is a critical locus for the generation and maintenance of a wide variety of circadian rhythms. This research program is designed to extend our knowledge of the neuroanatomical, neurophysiological and neuropharmacological organization of the SCN and its associated afferent and efferent structures. Using rats, cats and squirrel monkeys, neuroanatomical experiments are planned to identify the source of afferents to and outputs from the SCN. Particular attention will be paid to the retinohypothalamic tract (RHT). The retrograde transport of horseradish peroxidase (HRP) following intra SCM injection will identify the characteristics (soma size, dendritic morphology and retinal distribution) of those ganglion cells whose axons constitute the RHT. Further, the anterograde transport of HRP following intraocular injections will define the pattern of termination of the RHT in and around the SCN. Neurophysiological experiments on single units recorded from the SCN will be performed to characterize inputs to these cells. Photic stimulation of the retina and electrical stimulation of the RHT and other CNS afferents will be used to characterize the physiological responses and organization of SCN neurons. Neuropharmacological manipulations, both systemic and microiontophoretic, of SCN unit activity are planned to evaluate the functional neurochemical networks present in the SCN. Responses to cholinergic, dopaminergic, serotonergic and gabaergic stimulation will be examined. Other neurotransmitter systems may be examined contingent on the outcome of these and other studies. Moreover, the neuromodulatory role of these neurochemical systems on RHT input and SCN unit activity will be evaluated. Microiontophoretic deposition of HRP will be used to carefully map the neural organization of these cells within the SCN as well as their individual morphology. Thus, this multi-discipline, multi-species research program will provide further information on both the functional organization of the SCN and the complex neural network of CNS structures to which the SCN is connected. These studies should more completely define the role of the SCN in the mammalian circadian timing system and possibly identify the location of additional pacemakers coupled to the SCN. Such information will be invaluable in studying such applied problems as shift-work, sleepwake disorders and related aspects of mental health.